ABSTRACT
Objective:To assess the influence of glimepiride on the plasma concentrations and antihypertensive effects of losartan and its active metabolite losartan carboxylic acid(E-3174) in the patients with type 2 diabetes mellitus and hypertension. Methods:Pragmatic randomized controlled trial was used in the clinical study. Forty-five patients were enrolled and randomized into glimepiride group and the control group. Losartan was used as the antihypertensive drug in the two groups. After two-week interference,the plasma concentrations of losartan and its active metabolite E-3174 were determined using an LC-MS/MS method and the reduction of hyperten-sion was measured. Results:The plasma trough concentrations of losartan in glimepiride group was not higher than those in the control group,and those of E-3174 in glimepiride group was not lower than those in the control group. Additionally,the reduction of hyperten-sion was similar in the two groups. Conclusion: Glimepiride does not influence the plasma concentrations and the antihypertensive effects of losartan and its active metabolite E-3174 in the patients with type 2 diabetes mellitus and hypertension, suggesting no drug-drug interactions between them. Owing to the small sample,large clinical trial should be performed to confirm the above conclusion.
ABSTRACT
Objective:To systematically review the influence of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitors in the treatment of peptic ulcer in Chinese subjects. Methods:Such databases as SinoMed, CNKI, WanFang data, CQVIP, PubMed and Embase were electronically searched for the clinical studies on CYP2C19 genetic polymorphisms, proton pump inhibitors and peptic ulcer. According to the inclusion and exclusion criteria, the literatures were screened out, the data were extracted, and the methodological quality of the included studies was also examined. Meta-analysis was then performed using RevMan 5. 3 and Stata 13. 0 software. Results: A total of 8 studies involving 1197 Chinese subjects were included. The results of meta-analysis showed that CYP2C19 genetic polymorphism of patients was significantly associated with the healing rate of peptic ulcer treated with proton pump in-hibitors. No thinking about the type of proton pump inhibitors, the peptic ulcer healing rate for extensive metabolizer ( EM) phenotype was remarkably lower than that for intermediate metabolizer (IM) phenotype (OR=0. 63, 95％CI:0. 46-0. 86, P0. 05). Subgroup analysis further showed that only in omeprazole treatment, the peptic ulcer healing rate for EM phenotype was remarkably lower than that for IM phenotype (OR=0. 59, 95％CI:0. 36-0. 97, P<0. 05), or PM phenotype (OR=0. 29, 95％CI:0. 13-0. 62, P<0. 05), respectively. However, no differ-ence was found between IM and PM phenotype. The similar trends were not showed in the other proton pump inhibitors, including rabe-prazole, esomeprazole and ilaprazole. Conclusion:CYP2C19 genetic polymorphism only affects the efficacy of omeprazole for the thera-py of peptic ulcer, while shows no influence on the efficacy of the other proton pump inhibitors in Chinese subjects. Therefore, patients with peptic ulcer should receive genetic testing of CYP2C19 polymorphisms before the use of omeprazole.